Our laboratory has reported the correction of neutrophil NADPH oxidase function by retroviral-mediated gene transfer (RMGT) in murine X-linked chronic granulomatous disease (X-CGD). Few studies, however, have used nonmyeloablative conditioning in conjunction with RMGT. Promising methods of decreased intensity conditioning include low dose irradiation and antimetabolite conditioning. Preliminary studies using syngeneic mice transplanted with fresh marrow cells indicate that high levels of donor cell chimerism can be achieved with low-dose radiation or 5-fluorouracil-based conditioning regimens. Early data from experiments in which low-dose radiation-conditioned X-CGD recipients were transplanted with retrovirus-transduced X-CGD marrow cells show that gene-corrected neutrophils can be detected by NBT assay for NADPH oxidase activity reconstitution 4 months posttransplant, although these levels are much lower than the 50%-70% gene-corrected cell detected in lethally irradiated recipients. Transplantation of retrovirus-transduced marrow cells into 5-fluorouracil conditioned hosts is also being explored.